Risk factors for disease progression in patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH): a systematic analysis of expert opinion.

Disease progression has become an important issue for the management of lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). Although several risk factors have been identified, no specific patient risk profiles have been established that can be useful in the day-to-day management of LUTS/BPH. In this study, an international panel of urologists developed a risk classification based on the attribution of a risk score to 243 unique patient profiles. From the perspective of clinical decision making, it was concluded that postvoid residual, symptom severity and maximum flow rate are the most relevant determinants of the risk of disease progression.

Phytotherapy in the management of benign prostatic hyperplasia.

Phytotherapeutic agents have gained widespread usage in the treatment of benign prostatic hyperplasia/lower urinary tract symptoms. They are marketed as over-the-counter medications in the United States and by prescription in many European countries. Although numerous mechanisms of action have been postulated, it is uncertain which of these are responsible for their clinical response. The efficacy of these agents has not been conclusively proven. Almost all the studies with these products have not been placebo-controlled, double-blind trials of at least 6 months' duration. Thus, the magnitude of the clinical effect is uncertain. It is impossible to compare the phytotherapeutic agents-either the single or multiple extract products-because manufacturers use different extraction processes. So each agent/product must be studied individually. Until more appropriately conducted trials are undertaken, the efficacy of phytotherapeutic agents will remain unproven.

Saw Palmetto Berry as a Treatment for BPH.

Phytotherapeutic agents are often prescribed in Europe for the treatment of benign prostatic hyperplasia with lower urinary tract symptoms and are commonly used in the United States in over-the-counter preparations. Saw palmetto berry is the most popular of these agents, and in vitro some studies suggest that liposterolic extract of the plant has antiandrogenic effects that inhibit the type 1 and type 2 isoenzymes of 5alpha-reductase; however there are no clinical studies that show any decrease in serum dihydrotestosterone or prostate-specific antigen. Its efficacy in the treatment of lower urinary tract symptoms has not been conclusively proven. Clinical efficacy was suggested by a meta-analysis of Permixon, a formulation of saw palmetto, but the meta-analysis was done on suboptimal studies. One trial supports the equivalency of Permixon to finasteride in treating moderate to severe symptoms of benign prostatic hyperplasia, with less decrease in sexual function. However, without a control/placebo arm, the actual efficacy of the agents cannot be determined. Other than occasional gastrointestinal upset, no other side effects have been reported.

Phytotherapy for chronic prostatitis.

Chronic prostatitis is a poorly defined condition that is difficult to treat; there are therefore multiple therapies. Although there is a paucity of trials using phytotherapeutic agents, plant extracts have been postulated to have anti-inflammatory effects that might be useful in the treatment of chronic prostatitis. More placebo-controlled trials of longer duration in this condition are needed to ascertain whether there is a significant benefit to the use of phytotherapeutic agents for chronic prostatitis.

Economic analysis of finasteride: a model-based approach using data from the Proscar Long-Term Efficacy and Safety Study.

Benign prostatic hyperplasia (BPH) is one of the most common medical conditions in older men in the United States. BPH is often associated with a reduction in quality of life and may progress to acute urinary retention (AUR), the inability to pass any urine. Recently, a 4-year placebo-controlled clinical trial known as the Proscar Long-Term Efficacy and Safety Study (PLESS) demonstrated that finasteride use reduces the risk of developing AUR by 57% and the need for BPH-related surgery by 55%. The economic implications of these findings were investigated using a model-based decision-analytic approach to compare finasteride with both watchful waiting and alpha-blocker therapy. The modeling used the longest-term published controlled data concerning alpha-blockers, which were for the alpha-blocker terazosin. The base case considered a 64-year-old man (the mean age of a PLESS patient) with prostatic enlargement on digital rectal examination and moderate-to-severe symptoms of BPH. The model suggested savings in surgical and AUR costs with finasteride versus watchful waiting, with an estimated 25% of total finasteride costs recouped in savings on surgical events avoided in the first year. Over 2 years, the expected cost per patient starting finasteride therapy was $2304, whereas the expected cost per patient starting terazosin was $2334. Analyses also explored the variation in economic results by baseline levels of prostate-specific antigen (PSA), a proxy for prostate volume. For patients with PSA levels > or =1.4 ng/mL, expected 2-year costs with finasteride and terazosin were $2342 and $2479, respectively. For patients with PSA levels > or =3.3 ng/mL, expected 2-year costs with finasteride were $373 less than with terazosin ($2347 vs $2720). Results were robust over a range of model assumptions and cost estimates. The analyses illustrate that all medical interventions, including watchful waiting, have associated costs. Finasteride shows cost offsets compared with watchful waiting and cost savings compared with terazosin over 2 years. Finasteride appears to be more economical in men with higher PSA levels.

Effects of terazosin therapy on blood pressure in men with benign prostatic hyperplasia concurrently treated with other antihypertensive medications.

OBJECTIVES: To review and assess the cardiovascular safety of the alpha1-blocker terazosin when used to treat symptomatic benign prostatic hyperplasia (BPH) in patients taking concurrent antihypertensive medications. METHODS: This retrospective analysis focused on blood pressure changes and blood pressure-related side effects in 555 of 2084 patients randomized to either terazosin or placebo in the Hytrin Community Assessment Trial (HYCAT) study who were following either single or combination antihypertensive regimens (treated patients). We also compared results in normotensive and hypertensive patients, whether treated or not. RESULTS: The addition of terazosin lowered mean systolic blood pressure by 5.3 mm Hg for untreated patients and 6.7 mm Hg for treated patients. For patients hypertensive on entry, mean reductions in systolic blood pressure in those untreated and treated were 12.1 and 11.1 mm Hg, respectively. The addition of terazosin to an existing antihypertensive regimen had its greatest impact (a mean reduction of 12.3 mm Hg) in those receiving diuretic therapy alone. Diastolic pressure changes followed a similar pattern. The incidences of blood pressure-related side effects in patients on terazosin were comparable between untreated (13.5%) and treated patients (14.3%), as were premature withdrawal rates, with 4.2% of untreated patients and 4.5% of treated patients withdrawing due to blood pressure-related side effects. CONCLUSIONS: Terazosin can be safely used to treat patients with symptomatic BPH regardless of their blood pressure status and antihypertensive regimen. Terazosin may be safely added to ongoing antihypertensive therapy.

Review of recent placebo-controlled trials utilizing phytotherapeutic agents for treatment of BPH.

BACKGROUND: In order to assess the efficacy of phytotherapeutic agents for the treatment of benign prostatic hyperplasia (BPH), a review of recently published double-blind placebo-controlled trials was undertaken. METHODS: Only those studies reviewed by the Other Medical Therapies Committee of the Fourth International Consultation on BPH were included. RESULTS: These studies suggest a possible benefit for the use of phytotherapeutic preparations in the treatment of BPH. CONCLUSIONS: These studies need to be confirmed in larger long-term placebo-controlled studies in order to ascertain the true efficacy of these agents.

Use of magnetic resonance urography.

OBJECTIVES: Magnetic resonance urography (MRU) is a new technique that uses heavily weighted T2 coronal images with fat suppression pulse. Urine appears white on MRU, resembling an intravenous urogram (IVU). Contrast agents are not necessary. This study describes the use of MRU in the diagnosis and treatment of patients with hematuria. METHODS: One hundred six patients with microscopic or gross hematuria and 6 normal volunteers underwent MRU between 1992 and 1995. A modified, heavily weighted T2 technique with intravenous administration of furosemide and ureteral compression was used. Thirty-two patients had other imaging techniques as well for comparison. RESULTS: MRU provided high-resolution images in almost all cases; 73 (69%) had a normal MRU. Significant findings in the 33 patients with abnormalities included renal cysts in 17 (51%), renal cell carcinoma in 6 (18%), transitional cell carcinoma in 5 (15%), ureteropelvic junction obstruction in 3 (9%), and stones causing obstruction in 6 (18%). Five patients with renal failure also had good visualization of the entire urinary tract. MRU was comparable to other imaging modalities except in identifying nonobstructing calculi. CONCLUSIONS: MRU provides an alternative to conventional imaging of the urinary tract, especially in those patients who have contraindications to ionizing radiation and contrast agents. Improvements in resolution, technique, and cost have to be addressed before it can be used regularly in urologic practice.

Phytotherapy in the treatment of benign prostatic hyperplasia.

There are numerous plant extracts that have been used for the treatment of benign prostatic hyperplasia and voiding dysfunction. While some extracts show promise, their efficacy has not been adequately proven in long-term, double-blind, placebo-controlled trials. In addition, the mechanism of action remains poorly defined.

Penile trauma: an etiologic factor in Peyronie's disease and erectile dysfunction.

PURPOSE: It has been postulated that trauma to either the partially or fully erect penis is a potential cause of Peyronie's disease. In addition, it has been proposed that engaging in sexual relations with a partial erection due to mild impotence is a risk factor for the development of Peyronie's disease. This study was performed to determine whether patients with either Peyronie's disease or non-Peyronie's disease impotence had an increased rate of penile trauma compared with potent controls. MATERIALS AND METHODS: We mailed surveys to 207 men who had been seen for management of Peyronie's disease, 250 impotent men without Peyronie's disease, and 275 age-matched urologic patients without a history of either impotence or Peyronie's disease. The survey inquired whether the individual had a history of penile trauma to the flaccid or erect phallus or injury during sexual intercourse. In addition, patients were questioned whether they had been engaging in sexual relations with a partial erection. RESULTS: The mean age of the impotent patients was slightly less than both the Peyronie's disease patients and controls. A similar response rate to the survey was found among the 3 groups. The mean duration of illness was 6 years for Peyronie's disease and 10 years for impotence. The frequency of penile trauma of any kind was significantly greater in both the Peyronie's disease (40%) and impotence (37%) patients than in the controls (11%). There was no significant difference between the Peyronie's disease and impotence groups. However, the Peyronie's disease patients had a lower frequency of attempting sexual relations with a partial erection than the 2 other groups. CONCLUSIONS: The results of this survey demonstrate a significantly higher incidence of penile trauma in both impotent patients and patients with Peyronie's disease compared with controls. This study demonstrates an association between penile trauma and both Peyronie's disease and impotence. The reduced incidence of engaging in sexual relations with a partial erection among the Peyronie's disease patients implies that partial impotence is not a predisposing factor for Peyronie's disease.

Coadministration of tamsulosin and three antihypertensive agents in patients with benign prostatic hyperplasia: pharmacodynamic effect.

Tamsulosin, an alpha 1A-adrenoceptor antagonist, has recently been approved to treat patients with symptomatic benign prostatic hyperplasia (BPH). Tamsulosin is highly selective for prostatic receptors with minimal affinity for vascular receptors. Therefore, it should have little effect on blood pressure and should not potentiate other agents' antihypertensive activity. To test this hypothesis, we conducted three randomized, double-masked, placebo-controlled studies to evaluate how coadministration of tamsulosin would affect the pharmacodynamic profiles of nifedipine, enalapril, and atenolol. Each study enrolled 12 hypertensive men aged 45 years or older whose blood pressure was being controlled with maintenance doses of nifedipine (study 1), enalapril (study 2), or atenolol (study 3). All 36 subjects were treated with placebo for 5 days and then randomly assigned to either placebo (control group) or tamsulosin therapy (0.4 mg/d for 7 days followed by 0.8 mg/d for 7 days) in addition to continuing their maintenance antihypertensive therapy. Blood pressure and pulse rate were monitored over a 24-hour period on study days 4, 11, and 19. Coadministration of tamsulosin in these small studies had no clinically significant effects on the pharmacodynamic action of nifedipine, enalapril, or atenolol; it produced no clinically significant differences in pulse rate and blood pressure, did not alter electrocardiographic or Holter monitoring results, and did not cause increased side effects. Coadministration of tamsulosin with the three antihypertensive agents studied had a favorable safety profile. Our results in these small studies indicate that the dose of nifedipine, enalapril, or atenolol did not require adjustment in patients given tamsulosin, which may give tamsulosin an advantage over other alpha-blocking agents used to treat patients with BPH. Now that tamsulosin has been approved in the United States, further clinical use may confirm these findings.

The effects of prostatic manipulation on prostate-specific antigen levels.

Serum PSA determinations are an important part of the urologic evaluation for prostate cancer. DRE, TRUS, cystoscopy, and ejaculation have minimal effects on serum PSA levels. Prostatic massage, needle biopsy, TURP, and prostatitis can cause significant elevations of serum PSA (Table 1). These factors should be kept in mind for interpretation of PSA values.

Side effects of terazosin in the treatment of symptomatic benign prostatic hyperplasia.

In this report, we assess the safety of terazosin in the treatment of patients with symptomatic benign prostatic hyperplasia. We analyzed seven prospectively designed placebo-controlled trials involving 3,080 patients, 1,689 of whom received the study drug in doses ranging from 1 mg to 20 mg daily for a total of 1,282 patient-years of exposure. The most common side effects seen in treated patients were dizziness (10.7%), asthenia (7.5%), and peripheral edema (4.0%). These side effects were generally reported as mild and improved after cessation of therapy. The incidence of withdrawal from the study due to side effects was 14.5% in the treatment arm versus 11.4% in the placebo control arm. Also noted was a statistically significant decreased risk of urinary tract infection and myocardial infarction in the terazosin-treated group. This updated report confirms that terazosin can be administered safely to a population of men with symptomatic benign prostatic hyperplasia with minimal clinically significant side effects.

Urologic manpower issues for the 21st century: assessing the impact of changing population demographics.

OBJECTIVES: To evaluate the impact of changing population demographics on urologic staffing over the coming decades. METHODS: A model was constructed using data obtained from the U.S. Bureau of the Census for population projections; clinical studies to assess the percentages of men with symptomatic benign prostatic hyperplasia (BPH) and those undergoing prostatectomy; the American Medical Association regarding numbers and annual percent change of practicing urologists; and the American Urological Association regarding numbers of physicians completing residency training programs. Sensitivity analyses were performed varying both the rate of surgical intervention for symptomatic BPH and the annual increase in the number of practicing urologists. RESULTS: Regardless of variations in the surgical rate to as low as 4%, the average number of transurethral resections of the prostate gland/surgical interventions for BPH per urologist will increase by the year 2020 when compared with the known basepoint value obtained for 1990. Additionally, even with an annual net increase of 200 urologists per year, by 2020, the rapidly expanding population over 65 years of age will nearly offset even such a large increase in the number of practicing urologists. CONCLUSIONS: The greatest factor concerning future urologic staffing issues will be the changing population demographics. The need for urologic services will continue to rise. An oversupply of urologists can be avoided as long as the net increase does not exceed an average of 200 urologists annually.

Tamoxifen for flutamide/finasteride-induced gynecomastia.

OBJECTIVES: Current therapies for advanced prostate carcinoma lead to a marked decrease in serum testosterone levels, which renders patients impotent. In preliminary studies, combination therapy with flutamide and finasteride has been used as an alternative therapy for the treatment of prostate carcinoma because potency can be preserved. Both of these agents can cause gynecomastia and breast/nipple tenderness. METHODS: Six men being treated for advanced prostate carcinoma with flutamide/finasteride combination therapy developed painful gynecomastia, which was treated with tamoxifen 10 to 30 mg/day for 1 month. Clinical follow-up included breast measurements and determination of prostate-specific antigen (PSA), testosterone, and estradiol levels. RESULTS: While on this combination therapy for prostate carcinoma, 4 of 6 patients experienced a decrease in PSA level to less than 0.5 ng/mL. All patients remained potent. Serum testosterone increased in each patient who had a baseline level drawn. Estradiol levels were noted to be elevated in 4 of 6 patients at the time of evaluation for gynecomastia. After treatment with tamoxifen, circulating estradiol levels increased in 3 patients from 1.3 to 2.2 times the baseline level. Five patients experienced complete resolution of breast and nipple pain on tamoxifen 10 mg/day within the first month. The other patient had to be treated with 30 mg/day for 1 additional month, which subsequently resulted in pain resolution. CONCLUSIONS: These preliminary results suggest that low-dose tamoxifen is useful in treating painful gynecomastia for those patients on flutamide/finasteride combination therapy for advanced prostate carcinoma.

Giant malignant fibrous histiocytoma of the testis/spermatic cord: psychologic and possible etiologic complications of unethical Nazi medical experimentation.

This case of malignant fibrous histiocytoma of the testis/spermatic cord was found in a Holocaust survivor who was injected with an unknown substance in the left testicle while in Auschwitz concentration camp in 1943. Because malignant fibrous histiocytoma is a neoplasm rarely found in this location, with only 26 previously reported cases, a review of this entity was performed. A review of Nazi medical practices in the literature and through the Holocaust Museum research department was undertaken in an attempt to ascertain identification of the unknown substance injected into this patient; however, exact identification of the Auschwitz experiment or experimenter could not be determined. A left radical orchiectomy was performed, and subsequent histolopathologic review revealed a well-encapsulated 27 x 22 x 17-cm malignant fibrous histiocytoma. The left testis was not clearly identified due to necrosis of the tumor. This is the largest malignant fibrous histiocytoma of the spermatic cord/testis recorded in the literature to date. Based on the unusual location and size, the intratesticular injection probably contributed to the tumor development and certainly caused the patient's delay in seeking medical treatment.

Phytotherapy in treatment of benign prostatic hyperplasia: a critical review.

Phytotherapeutic agents have enjoyed widespread use, especially in Europe, for the treatment of BPH. With the recent proliferation of nutrition and vitamin stores in the United States, use of these agents has greatly increased. Although SPB extract is the most extensively studied of the phytotherapeutic agents used for BPH, no well-defined mechanism of action has been proposed. Evidence for an antiandrogenic or antiestrogenic effect is conflicting, and there are no clinical data suggesting an effect on 5-alpha-reductase activity. Furthermore, clinical trials with SPB have largely been uncontrolled and are thus of limited value in ascertaining the true clinical impact of this agent. Double-blind, controlled studies with SPB also have limitations in that most were of very short duration (none longer than 3 months) and did not provide entry or exclusion criteria. In addition, standardized symptom scores were not utilized. Only two of seven studies showed an appropriate placebo response, and the results and conclusions of both these studies were contradictory. The best and most convincing study of the efficacy of phytotherapeutic agents (using Harzol) was recently published in the Lancet. This study was rigorous and matched in design and format with pharmaceutical industry trials. A mild but appropriate placebo response was detected, which further validates the study. However, a prior placebo-controlled study showed no efficacy of beta-sitosterol-beta-D-glucoside. This dichotomy of results possibly reflects the different composition of the agents tested. This is a major confounding factor in this field of study, especially because the active ingredients are unknown. Standardization of the compounds is needed to compare and assess accurately the effect of the different extracts.